It is known that radiolabeled antibodies to carcinoembronic antigen (CEA) can be used to localize tumors. U.S. Pat. No. 3,927,193, to Hansen et al, discloses such a method, but provides examples of its use only in animals. The method described in this patent does not explain how tumors may be visualized in a situation where radioactivity is also present in other sites of the body, such as blood, other body fluids and certain tissues, particularly heart and liver, which can prevent precise discrimination of the radioactivity associated with the sites of tumor. Early clinical studies reported by Reif et al, J. Surg.Oncol., 6, 133 (1974) and Mach et al, Europ. J. Cancer, Suppl. 1, 113 (1978) failed to show tumor localization in humans with radioactive anti-CEA antibodies.
Goldenberg et al, in an article in the New England Journal of Medicine, 298, 1384 (1978), reported success in clinical trials of tumor detection and localization by scintillation scanning of patients receiving radiolabeled antibodies to CEA. In that reference, it was noted that there was a problem in both animal and human studies in distinguishing specific radioantibody activity from blood-pool background activity, and that special scanner subtraction techniques with other radionuclides were considered essential for unequivocal tumor localization using this method. The antibody preparation used in the reference was 70% immunoreactive with CEA. The reference further notes that the absence of CEA in normal hamster tissues precludes extrapolation to man, in whom the antigen usually circulates in increased levels in patients with cancer, and is present in lesser quantities in certain normal tissues. The subtraction technique used to permit localization using this scintigraphic method involved injection of Tc-99m-pertechnetate and Tc-99m-labeled human serum albumin prior to each imaging scan. The data obtained were stored in a minicomputer capable of generating digital images of the labeled antibody alone, the Tc-99m labeled species together, and sums and differences of these various values.
Even this most recent and successful tumor localization and detection process has certain disadvantages which limit its resolution, it efficiency and its practicability. The use of a different radionuclide attached to a carrier having kinetics of transport and distribution different from an antibody in the subtraction technique used to distinguish tumor localized antibody from background activity is not an ideal procedure. Furthermore, the need to inject these materials prior to each photoscan is an inconvenience, it not an ideal procedure, and exposes the patient to increased levels of radioactivity. U.S. Pat. No. 3,927,193 teaches that the anti-CEA antibody should not be labeled to a degree which might interfere with the activity of the antibody, a limitation which was not questioned in the later references discussed above. However, this limits the resolution of the method and requires larger quantities of antibody for image detection.
Tumor radiotherapy using labeled antibodies has been suggested by many, and an indication of its success in a single multimodal therapeutic clinical use is reported by Order, Radiol., 118, 219 (1976). The use of boron-labeled antibodies in therapy is reported by Hawthorne et al., J. Med. Chem., 15, 449 (1972), but the combined incorporation of boron and a radioisotope for localization is not suggested.
A need therefore continues to exist for a method of tumor detection and localization which can achieve high resolution and which avoids the aforementioned disadvantages.